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Scientists Erased Cocaine-Cue Memories In Rats And It Prevented Relapse

The brain associates specific cues with behaviors. This is called classical conditioning and it was first discovered by Pavlov while observing dogs in the 1890s. An example of classical conditioning in humans is, for instance, the smell of freshly brewed coffee-making you want to drink a cup. It’s when an environmental cue triggers a behavior (action) or desire (urge). Breaking the links between cues and memories is a well-known strategy in treating phobias, addiction, and PTSD.

It’s not so easy to do though. Even though they understand what is causing the behavior, it’s not like turning a switch on and off to make it stop. The problem still stands that 40-60 percent of all people treated for substance use disorders, relapse. The method they have been using, commonly known as ‘exposure therapy’, is obviously not very effective at treating addiction. Why? Because context matters.

In the controlled setting, such as a doctor’s or therapist’s office, the therapy will seem to be working. Then, the moment a person suffering from addiction is faced with the cue in the outside world, the brain fires off the same neurons connected to drug-seeking behavior.

But now, The University of Pittsburgh School of Medicine has opened up a potential avenue for developing more effective therapies to prevent relapse. Their new research shows that by disrupting memories which associate environmental cues with drug use, they can significantly reduce drug-seeking behaviors in rats. The Study has been published in Cell Reports.

Mary Torregrossa, Ph.D., associate professor of psychiatry at Pitt’s School of Medicine and senior author of the study, said:

“While we’ve always known that the brain forms these cue-associated memories, the specific circuits have never been clearly identified. We’ve found a central piece in the cue-memory puzzle, and we also show that taking out that piece in a substance use scenario can help reverse relapse-like behaviors.”

The Study

  • The scientists used a rat model of cue-associated relapse.
  • First, they got the rats addicted to cocaine. They did this by providing the rats with a dose whenever they pressed a lever. When the lever was pressed, it also triggered a tone to beep and a light to flash, simultaneously. This created a memory which linked sound and visuals to a dose of drugs.
  • Over time, the rats began to press the lever whenever they heard the tone and saw the light — a sign that the stimuli triggered the rats’ desire for the drug.
  • Then, they’d flash the light and sound, but when the rat pressed the lever nothing would happen. This was to break the connection between the triggers and the drug-seeking behavior. It worked. After a while, the rats stopped pressing the lever, even when the triggers went off.
  • However, when they changed the rats’ environment by moving them into a different space, the animals once again began pressing the lever in response to the tone and light.
  • The whole scenario is the same as with humans in therapy nowadays.

Solution

Throughout the experiment, they monitored and studied the rats’ brains.

Cocaine memory
“Illustration of the rat brain circuit connections responsible for forming memories that associate cocaine use with external cues.”  (CREDIT: Adapted from Rich, T.M., et al Cell Reports/Mary Torregrossa)

The researchers were able to identify connections between two parts — the medial geniculate nucleus and the lateral amygdala — as playing an essential role in forming the memories that made the animals associate the tone and light with cocaine.

Researcher Matthew Rich said in a press release:

“It made sense to us because the amygdala is where emotional memories are formed. It receives sensory input and associates that input with what we feel when the cues are presented to us.”

They used a light-based technique known as “optogenetics” to control the neurons between the two parts of the brain, effectively erasing memories linked to cocaine use in some of the rats.

The technique worked on the rats. They pressed the lever significantly fewer times when exposed to the tone and light. Even when they placed the rats in a new environment, the decreased desire for cocaine persisted.

Conclusion

This treatment could be extremely beneficial. Currently, as many as 70 percent of cocaine users relapse within 90 days. If they can use this therapy to erase the memories linked to cocaine use, like they were able to do with the rats, they can decrease drug-seeking behavior and help humans overcome a drug habit.

Researcher Mary Torregrossa said:

“In the long-term, these findings may help us develop drugs or approaches like deep brain stimulation to specifically target these memories strengthened by substance use and improve the success of exposure therapy to prevent relapse.”

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